title: Pharmacokinetics and metabolism of 4-O-methylhonokiol in rats.
abstract: The purpose of this study was to characterize the pharmacokinetics and metabolism of 4-O-methylhonokiol in rats. The absorption and disposition of 4-O-methylhonokiol were investigated in male Sprague-Dawley rats following a single intravenous (2 mg/kg) or oral (10 mg/kg) dose. Its metabolism was studied in vitro using rat liver microsomes and cytosol. 4-O-Methylhonokiol exhibited a high systemic plasma clearance and a large volume of distribution. The oral dose gave a peak plasma concentration of 24.1±3.3 ng/mL at 2.9±1.9 h and a low estimated bioavailability. 4-O-Methylhonokiol was rapidly metabolized and converted at least in part to honokiol in a concentration-dependent manner by cytochrome P450 in rat liver microsomes, predicting a high systemic clearance consistent with the pharmacokinetic results. It was also shown to be metabolized by glucuronidation and sulfation in rat liver microsomes and cytosol, respectively. 4-O-Methylhonokiol showed a moderate permeability with no apparent vectorial transport across Caco-2 cells, suggesting that intestinal permeation process is not likely to limit its oral absorption. Taken together, these results suggest that the rapid hepatic metabolism of 4-O-methylhonokiol could be the major reason for its high systemic clearance and low oral bioavailability.
authors.affiliation: Bio-Evaluation Center, KRIBB, Chungbuk, Republic of Korea; College of Pharmacy, Chungbuk National University, Chungbuk, Republic of Korea.
authors.forename: Hyung Eun
authors.initials: HE
authors.lastname: Yu
authors.forename: Soo Jin
authors.initials: SJ
authors.lastname: Oh
authors.forename: Je Kyung
authors.initials: JK
authors.lastname: Ryu
authors.forename: Jong Soon
authors.initials: JS
authors.lastname: Kang
authors.forename: Jin Tae
authors.initials: JT
authors.lastname: Hong
authors.forename: Jae-Kyung
authors.initials: JK
authors.lastname: Jung
authors.forename: Sang-Bae
authors.initials: SB
authors.lastname: Han
authors.forename: Seung-Yong
authors.initials: SY
authors.lastname: Seo
authors.forename: Young Heui
authors.initials: YH
authors.lastname: Kim
authors.forename: Song-Kyu
authors.initials: SK
authors.lastname: Park
authors.forename: Hwan Mook
authors.initials: HM
authors.lastname: Kim
authors.forename: Kiho
authors.initials: K
authors.lastname: Lee
mesh_terms: D000042:Absorption; D000818:Animals; D001682:Biological Availability; D001713:Biphenyl Compounds / Q000378:metabolism* / Q000493:pharmacokinetics*; D018938:Caco-2 Cells; D002463:Cell Membrane Permeability; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006801:Humans; D017705:Lignans / Q000378:metabolism* / Q000493:pharmacokinetics*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C542058:4-O-methylhonokiol; D001713:Biphenyl Compounds; D017705:Lignans; D003577:Cytochrome P-450 Enzyme System
keywords: 4-O-methylhonokiol; honokiol; metabolism; neolignan; pharmacokinetics